This study was planned to assess the relationship of perioperative glycemic control to the subsequent risk of infectious complications and to compare early clinical outcomes of coronary artery bypass surgery in diabetics with nondiabetics in a single center. A total of 1090 adults who underwent coronary artery surgery in a five year period were included in a retrospective cohort study based on available chart review. Of 1090 patients, 400 had type II diabetes mellitus. Intraoperative and postoperative blood glucose levels in diabetic group were manipulated by means of a continuous insulin infusion. Data of pre- and postoperative blood glucose levels were evaluated with respect to postoperative infection risk for diabetics. Risks of early mortality, cerebrovascular accident, and postoperative infection in diabetic patients were compared with the nondiabetic group. High preoperative mean glucose levels were the main risk factor for the development of postoperative infection (p = 0.012 and p = 0.028 for the mean glucose levels 1 and 2 days before operation, respectively). For diabetic group, of 400 patients 20 (5%) were diagnosed to have postoperative infection (superficial sternal wound in 3 (0.75%), donor site infection in 4 (1%), mediastinitis in 5 (1.25%), urinary tract infection in 6 (1.5%), and lung infection in 2 (0.5%) patients). The diabetic group had significantly higher prevalence of mediastinitis, donor site infection, urinary tract infection and total infection (p values were 0.048, 0.013, 0.009, and 0.044, respectively). Early mortality was higher among diabetics than in nondiabetics (1.73% vs 3%, p = 0.048) but the risk of cerebrovascular accident in diabetics was not greater than in nondiabetics in early period. In patients with diabetes who undergo coronary artery bypass surgery, preoperative hyperglycemia is an independent predictor of short-term infectious complications and total length of stay in hospital.

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Progesterone markedly inhibitis the functions of human macrophages and T lymphocytes, and acts as an immunosuppressant during pregnancy. It is important to examine progesterone metabolites to understand the overall bioactive properties of this sex steroid. However, progesterone metabolism has not been examined in human immune cells. The human leukemic monoblast U937 cell line exhibits monocytic lineage and provides a valuable model to analyze monocyte-macrophage differentiation. Therefore, in this study, we analyzed progesterone metabolism in U937 cells by thin-layer chromatography. Progesterone was metabolized to 5α-pregnan-3β,6α-diol-20-one via 5α-dihydroprogesterone and 5α-pregnan-3β-ol-20-one, and 5α-pregnan-3β,20α-diol was also detected as a final metabolic product via 20α-dihydroprogesterone and 5α-pregnan-20α-ol-3-one. 5α-reduction (5α-reductase type 1) and 20α-reduction were involved in the first step of metabolism. To identify the enzyme responsible for the 20α-reduction, we screened an U937 cDNA library, and obtained a clone (1.2 kb), which was identical to the human hepatic bile acid-binding protein or 20α-hydroxysteroid dehydrogenase (20α-HSD). 293 cells transfected with this cDNA demonstrated marked 20α-reduction of progesterone to 20αDHP, but 20α-oxidative, 3α-HSD or 17β-HSD activity was found to be negligible. In experimental animals, the importance of 20α-HSD has been reported to be involved in the protection of immune cells from the toxic effects of progesterone. Therefore, our present data suggest that 20α-HSD plays an important role in the reguation of progesterone actions in human immune cells.

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The effects of diabetes and exercise training on the activity of pyruvate dehydrogenase (PDH) complex in skeletal muscle were examined in rats. Male Sprague-Dawley rats were divided into four groups as follows: non-diabetic sedentary, non-diabetic trained, diabetic sedentary, and diabetic trained groups. Diabetic rats were prepared by a boulus injection of intravenous streptozotocin (50 mg/kg body weight). Exercise training was performed by having rats run on a treadmill at a speed of 25 m/min for 45 min/day, 6 days/wk for 4 wks. Exercise training decreased serum concentrations of glucose and non-esterified fatty acid in diabetic rats. GLUT4 content in skeletal muscle in sedentary rats was significantly decreased by diabetes; however, exercise training significantly increased the GLUT4 content in diabetic rats. The total and actual activities and the proportion of actual activity of the PDH complex were decreased in diabetic sedentary rats. Exercise training did not affect the total activity of the PDH complex in non-diabetic rats, whereas it incresed the total activity in diabetic rats to the same level as that in non-diabetic rats. In diabetic rats, exercise training tended to increase the proportion of actual activity of the PDH complex from 2.7 ± 0.4% to 4.7 ± 0.8%, although the proportion of actual activity in non-diabetic rats was decreased by exercise training. The present study suggests that exercise training may improve glucose metabolism in the skeletal muscle of streptozotocin-induced diabetic rats probably through the mechanisms of increasing both GLUT4 content and the activity of the PDH complex.

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A 30-year-old female patient, diagnosed as having Graves’ disease in 1996, was treated with propylthiouracil (PTU) for 4 years. She developed a low-grade fever from December 1999. As myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) vasculitis is one of the adverse effects of PTU, we examined serum MPO-ANCA level and found it was positive, but cytoplasmic-ANCA (c-ANCA) was negative. There were no symptoms that indicated other diseases associated with MPO-ANCA. She was confirmed to be at 6 weeks gestation, and thyroid hormone levels were elevated at that time. We discontinued PTU and gave methyl-mercaptoimidazole (MMI), and the titer of MPO-ANCA fell along with fever. Therefore we estimated the case as probable MPO-ANCA positive vasculitis induced by PTU. MMI was also suspended because of the development of hepatic dysfunction. After thyroid function was normalized by administration of potassium iodide, she underwent subtotal thyroidectomy, and delivered a 2350 g infant at 38 weeks’ gestation, which was less than the normal birth weight of 2400 g. MPO-ANCA is considered to be one reason of low birth weight infant including hyperthyroidism. It is necessary to consider the appearance of the possibility of MPO-ANCA positive vasculitis in patients who are treated with PTU.

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The aim of this study was to clarify the pattern of β cell neogenesis in the alloxan-perfused, β cells-depleted segment of glucose intolerant mice induced by selective alloxan perfusion. First, duct cells proliferated in the perfused segment, then cells co-expressing multiple islet hormones and transcription factors such as PDX-1, Nkx2.2, Isl1, and Pax6 were observed in duct cells, and newly formed islet-like cell clusters (ICCs) containing β cells were recognized. In residual β cell-depleted islets, glucagon or somatostatin and PDX-1 double-positive immature endocrine cells were recognized. Glucagon or somatostatin, insulin and PDX-1 triple-positive cells then appeared and these cells appeared to undergo terminal differentiation into β cells. In conclusion, we demonstrated at least two different processes of β cell neogenesis, i.e., formation of new ICCs from ductal epithelium and redifferentiation of residual non-β islet cells in this model. In addition, transcription factors that appear in the processes of endocrine cell development may also play essential roles during β cell neogenesis from duct cells.

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In castrated male rats, a radiofrequency lesion was made in the dorsal raphe nucleus (DRL) and lordosis behavior was observed following treatment with estrogen. After the behavioral test, brains were removed and the contents of 5-HT and 5-HIAA in the forebrain were measured by high pressure liquid chromatography (HPLC). In the results, only 2 of 16 control males without brain surgery showed lordosis, and the mean lordosis quotient (LQ) was extremely low when compared to that in control females. In contrast, all male rats with DRL displayed lordosis and the mean LQ was higher than that of control males without brain surgery but lower than that in control females (P<0.001). In the DRL males, 5-HT and 5-HIAA contents in the septum (SPT), the preoptic area (POA), the ventromedial hypothalamus (VMH) and the striatum (STM) were lower than those in control male and female groups (P<0.001). These results suggest that the dorsal raphe nucleus prevents male rats from showing lordosis by serotonergic influence in the forebrain. In addition, HPLC results showed that levels of the 5-HT in the SPT, the POA and the VMH in the female group were higher than those in the control male group (P<0.05). In female rats, the POA (P<0.01) and the VMH (P<0.05) contained larger 5-HT than those in the SPT and the STM, but there were no difference of 5-HT contents in the male rat.

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